Details

Autor(en) / Beteiligte

• Westra, Harm-Jan
• Martínez-Bonet, Marta
• Onengut-Gumuscu, Suna
• Lee, Annette
• Luo, Yang
• Teslovich, Nikola
• Worthington, Jane
• Martin, Javier
• Huizinga, Tom
• Klareskog, Lars
• Rantapaa-Dahlqvist, Solbritt
• Chen, Wei-Min
• Quinlan, Aaron
• Todd, John A
• Eyre, Steve
• Nigrovic, Peter A
• Gregersen, Peter K
• Rich, Stephen S
• Raychaudhuri, Soumya

Titel

Fine-mapping and functional studies highlight potential causal variants for rheumatoid arthritis and type 1 diabetes

Ist Teil von

• Nature genetics, 2018-10, Vol.50 (10), p.1366-1374

Ort / Verlag

United States: Nature Publishing Group

Erscheinungsjahr

2018

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• To define potentially causal variants for autoimmune disease, we fine-mapped 76 rheumatoid arthritis (11,475 cases, 15,870 controls) and type 1 diabetes loci (9,334 cases, 11,111 controls) . After sequencing 799 1-kilobase regulatory (H3K4me3) regions within these loci in 568 individuals, we observed accurate imputation for 89% of common variants. We defined credible sets of ≤5 causal variants at 5 rheumatoid arthritis and 10 type 1 diabetes loci. We identified potentially causal missense variants at DNASE1L3, PTPN22, SH2B3, and TYK2, and noncoding variants at MEG3, CD28-CTLA4, and IL2RA. We also identified potential candidate causal variants at SIRPG and TNFAIP3. Using functional assays, we confirmed allele-specific protein binding and differential enhancer activity for three variants: the CD28-CTLA4 rs117701653 SNP, MEG3 rs34552516 indel, and TNFAIP3 rs35926684 indel.